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POLYMER DEGRADATION AND STABILITY · 2019 · IF 3.78

Fluorescent enhancement of polyethyleneimine nano-polymers and the application in cellar imaging

Lei Chen,Fang Raohao,Zhang Changchang,Liu Xiang,Zhang Changhua

Nano-polymers (NPs) with non-conjugated moiety emit bright fluorescence when irradiated by ultraviolet lights, which arouses extensive interests since they do not have traditional fluorophores or conjugated moieties. Although the mechanism was put forward in some reports and entitled as “crosslink enhanced emission” (CEE) the oxidation of starting material is also contributable for the enhanced fluorescence according to our researches. However this has been neglected until now. Herein, when aqueous solution of pure polyethyleneimine (PEI) was suffered from heating at 180° in air for 60 min crosslink of PEI molecules took place and produced PEI NPs. It emitted bright blue fluorescence and the quantum yield reached as high as 18.24% while PEI itself possessed none of fluorescence. Infrared, 1 H nuclear magnetic resonance and X-ray photoelectron spectra disclosed the oxidation of PEI during the lasting heating. And the image of transmission electron microscope confirmed the production of PEI NPs. When PEI NPs were prepared in the presence of hydrogen peroxide they performed a successive enhancement of fluorescent intensity, which demonstrated the oxidation of PEI contributed a lot for the fluorescent enhancement of PEI NPs. Experimental results also demonstrated that the PEI NPs have a potential application in cellar imaging on account of the lower cytotoxicity and the reactivity to the activated folic acid .

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JOURNAL OF LUMINESCENCE · 2019 · IF 2.961

Platinated porphyrin tailed with folic acid conjugate for cell-targeted photodynamic activity

Si Yao,Li Chen,Fang Jia,Xinzhi Sun,Huifang Su,Hongjian Liu,Lixia Yang,Zejiang Wang,Fengshou Wu,Kai Wang

For a precisely targeted photosensitizer , we designed and prepared a new platinated porphyrin ( Pt-Por-FA ) by Pt-Por tailed with folic acid ( FA ). The intercalation mode of Pt-Por-FA binding to ct-DNA was confirmed by UV–vis and fluorescent spectra. The singlet oxygen generation of Pt-Por-FA was evaluated through 2′, 7′-dichlorofluorescin (DCFH) method. The cellular uptake and the intracellular localization of Pt-Por-FA were studied upon A549 and HeLa cells through confocal laser scanning microscope. The results showed that the red fluorescence of porphyrin conjugate observed in HeLa cells [folate receptor (FR)–positive] was significantly stronger than that of A549 cells (FR-negative), indicating that Pt-Por-FA could target specifically the cancer cells with overexpression of FR via FR-mediated endocytosis. Pt-Por-FA successfully localized in the lysosomes of cancer cells, but Pt-Por without FA did not. Moreover, the cytotoxicity against HeLa and MDA-MB-231 cells was measured by MTT assay . The results demonstrated that Pt-Por-FA had minor cytotoxicity in the dark, but showed a obviously improving toxicity in presence of light. At the concentration of 20 μM Pt-Por-FA , the cell viabilities were only 12.0% and 26.4% with the IC 50 values down to 5 μm and 12 μm against HeLa and MDA-MB-231 cells, respectively. It suggests that Pt-Por-FA could be a precisely targeted photosensitizer with over-expression of a folate receptor.

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COLLOIDS AND SURFACES B-BIOINTERFACES · 2019 · IF 3.973

β-Cyclodextrin coated and folic acid conjugated magnetic halloysite nanotubes for targeting and isolating of cancer cells

Xiufang Li,Jian Chen,Hui Liu,Zhiwei Deng,Jianbing Li,Tao Ren,Ling Huang,Wenqing Chen,Yanjing Yang,Shian Zhong

The study developed a simple, effective and inexpensive strategy for capturing, enriching and detecting circulating tumor cells (CTCs) by using folic acid (FA) as the targeting molecule instead of antibodies. This work constructed magnetic halloysite nanotubes (MHNTs) coated with biocompatible β-cyclodextrin (CD), and conjugated to FA via a PEG-Ad linker, to specifically capture the FA receptor (FR)-overexpressing cancer cells. The capture efficiencies of [email protected] β [email protected] for the Skov3, Hela and A549 cancer cells were 96.3%, 97.0% and 95.6% respectively. In addition, the nanoparticles were able to capture very low numbers of the cancer cells (25–500 cells/mL) from PBS and whole blood, as well as selectively capture the cancer cells over normal HEK 293 T cells. Furthermore, the captured cells were viable and grew normally in vitro , indicating the future potential of downstream analyses. This approach can be adapted for different CTCs, once the tumor-specific surface markers are identified and the efficacy of targeting ligands is established. Taken together, FA-conjugated MHNTs nanoparticles are a highly promising tool for isolating CTCs for the diagnosis and treatment of cancer.

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Pharmaceutics · 2019 ·Vol. 11 ·期 11 ·584 · IF 4.773

Fabrication of Ion-Crosslinking Aminochitosan Nanoparticles for Encapsulation and Slow Release of Curcumin

Xiaoxiao Sun,Dongyan Yu,Zhuoyang Ying,Chuqiao Pan,Nan Wang,Fangfang Huang,Junhong Ling,Xiao-kun Ouyang

Curcumin (Cur) has anticancer activities but has poor stability, which can be improved using carrier materials. In this study, chitosan was aminated to increase the number of amino groups on its surface, modified with folic acid (FA), and then made into nanoparticles by ionic crosslinking. Owing to ion interaction, the negatively charged, non-toxic tripolyphosphate (TPP) interacted with the positively charged amino group on the aminated chitosan (AmCS) surface, producing FA-AmCS-TPP nanoparticles, which were then characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry (FT-IR), and thermogravimetric analysis (TGA). Their small particle size (175.2 ± 0.99 nm) and good surface positive potential (+42.4 mV) are beneficial for carrying antitumor drugs. We subsequently investigated whether coating of Cur by AmCS allows slow drug release by FA-AmCS-TPP nanoparticles in different pH environments, and estimated the Cur loading efficiency (EE-Cur). Our results showed that the cumulative release rate of Cur at 48 h was 56.2%, and that the EE-Cur reached 94.26 ± 0.91% with nanoparticles composed of 0.10 g AmCS, 10.0 mg FA, 10.0 mg TPP, and 15.0 mg Cur. Additionally, cytotoxicity experiments showed that the Cur/FA-AmCS-TPP nanoparticles had good targeting ability for tumor cells. Therefore, the non-toxic targeted composite nanoparticles had potential as a new antitumor agent that can overcome the limitations of Cur.Keywords:aminated chitosan;folic acid;nanoparticles;targeted delivery;curcumin

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Pharmaceutics · 2019 ·Vol. 11 ·期 11 ·582 · IF 4.773

Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis

Minglei Chen,Kambere Amerigos Daddy J.C.,Zhigui Su,Nida El Islem Guissi,Yanyu Xiao,Li Zong,Qineng Ping

Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&CAT-L. In vitro results revealed that FOL-MTX&CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&CAT-L may be used as an effective nanomedicine system for RA treatment.Keywords:rheumatoid arthritis;folate receptor;active targeting;reactive oxygen species-responsive drug release;methotrexate;catalase;oxygen-generation

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2019 · IF 4.784

Covalent immobilization and characterization of penicillin G acylase on amino and GO functionalized magnetic Ni0.5Zn0.5Fe2O4@SiO2 nanocomposite prepared via a novel rapid-combustion process

Qingmei Yu,Zhou Wang,Yewang Zhang,Ruijiang Liu

Magnetic Ni 0.5 Zn 0.5 Fe 2 O 4 @SiO 2 nanocomposite was prepared via the rapid combustion process, and its surface was modified to obtain amino-functionalized magnetic Ni 0.5 Zn 0.5 Fe 2 O 4 @SiO 2 -NH 2 nanocomposite. The modified nanocomposite was loaded on graphene oxide (GO), on which penicillin G acylase (PGA) was covalently immobilized. The structure for docking was visualized between PGA and penicillin G using the PyMol program, which revealed the configuration of the active site. Selections of immobilization conditions including immobilization concentration and time of fixation, were explored. The catalytic performance of the immobilized PGA was characterized. The immobilized and free PGA had the highest activity at pH 8.0 and 45 °C. Compared with the activity of the free PGA, the activity of the immobilized PGA was affected less by pH and temperature. The immobilized PGA exhibited the high-effective activity and good stability. V max and K m of immobilized PGA were 0.8123 mol·min −1 and 0.0399 mol·L −1 , respectively. Free PGA's V max and K m were 0.6854 mol·min −1 and 0.0328 mol·L −1 . Immobilized PGA remained >70% in relative activity after 9 successive cycles.

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ACS Biomaterials Science & Engineering · 2019 · IF 4.511

Folate Receptor-Mediated Renal-Targeting Nanoplatform for the Specific Delivery of Triptolide to Treat Renal Ischemia/Reperfusion Injury

Caili Huang,Tao Zeng,Jiawen Li,Lishan Tan,Xiulong Deng,Yanchao Pan,Qi Chen,Aiqing Li,Jianqiang Hu

Triptolide (TP) has been widely used in clinical medicine; however, it has created a dilemma due to its toxicity and nonspecificity. Here, we reported a biocompatible and high-efficiency renal-targeting nanoplatform for renal ischemia/reperfusion injury (IRI) therapy, in which the toxic drug of TP was encapsulated into folate (FA)-modified Pluronic F127/P123 nanoparticles (FPNPs). The TP-loaded FPNPs (TP-FPNPs) had good stability and could effectively reduce the cytotoxicity of TP. Compared with the Pluronic nanoparticles (PNPs) group, cellular uptake ability of FPNPs significantly improved because of folate receptor-mediated endocytosis effect. Ex vivo organ imaging and pharmacokinetic results indicated that FPNPs possessed high kidney selectivity and long retention time. The therapeutic effect of TP-FPNPs on renal IRI was more superior to that of free TP, such as lower acute tubular injury index (2.9-fold), renal function indexes of serum creatinine (4.3-fold), urea nitrogen (2.0-fold), and Western blotting (2.4-fold). Systemic toxicity assay suggested that TP-FPNPs had much lower nephrotoxicity, hepatotoxicity, and genital system toxicity than free TP. Thus, renal-targeting FPNPs will be a potential delivery platform of hydrophobic drugs for treatment of renal diseases.

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JOURNAL OF INORGANIC BIOCHEMISTRY · 2018 · IF 3.063

Synthesis and characterization of a flexible fluorescent magnetic Fe3O4@SiO2/CdTe-NH2 nanoprobe

Min Wang,Xiaofang Fei,Shaowu Lv,Ye Sheng,Haifeng Zou,Yanhua Song,Fei Yan,Qianlong Zhu,Keyan Zheng

In this study, we designed and synthesized two novel fluorescent magnetic nanoparticles . Fe 3 O 4 @SiO 2 -NH-GSH-CdTe (FSGC) (GSH = glutathione) nanoparticles were synthesized using amino-functionalized Fe 3 O 4 @SiO 2 nanoparticles and GSH-stabilized CdTe quantum dots (CdTe QDs), while flexible Fe 3 O 4 @SiO 2 -NH-GSH-CdTe-NH-NH 2 (FSGCN) nanoparticles were synthesized using the FSGC precursor and 1,6-hexamethylenediamine. These two kinds of nanoprobes exhibited excellent magnetic and fluorescent properties. By comparing the fluorescence quenching effect of folic acid (FA) on FSGC and FSGCN, we found that the quenching effect of FA on FSGC was acute and the process was too fast to determine the FA content. However, the quenching effect of FA on flexible FSGCN was mild and hence it could be used as a nanoprobe to determine FA concentration. At physiological pH, the fluorescence quenching effect of FA on the FSGCN nanoprobes was fitted according to the Stern–Volmer equation with a linear response in the concentration range of 0.14 to 4.20 μg mL −1 with a detection limit of 15.1 × 10 −9  g mL −1 (S/N = 3) under optimized experimental conditions. The proposed flexible nanoprobe was successfully used to determine the content of FA in folic acid tablets. Recovery was found to be in the range of 92.7%–105.6% with a relative standard deviation of 1.12%–3.84%. Owing to their good stability, environment-friendly characteristics, high selectivity, and good optical properties and biocompatibility, these nanoprobes have potential for usage in practical applications.

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ACS Applied Materials & Interfaces · 2018 · IF 8.097

Folic Acid-Functionalized Hybrid Photonic Barcodes for Capture and Release of Circulating Tumor Cells

Chengxin Luan,Huan Wang,Qi Han,Xiaoyan Ma,Dagan Zhang,Yueshuang Xu,Baoan Chen,Minli Li,Yuanjin Zhao

Recovery of circulating tumor cells (CTCs) from cancer patients by an efficient CTCs capture and release method can greatly increase their application in diagnostics and treatment of cancers. In this paper, we presented a folic acid (FA)-functionalized hybrid photonic barcode for capture and release of CTCs. The hybrid photonic barcodes were formed by two nano-ordered parts, poly(ethylene glycol) diacrylate (PEGDA) inverse opal structure for sustaining integrity and methacrylated gelatin (GelMA) gel filler for conjugating FA molecules to mediate cell capture. The nano-ordered structures of the hybrid photonic barcodes not only increased contact area, but also decreased steric hindrance among FA molecules. Thus, the topographic interaction between the barcodes and CTCs was greatly enhanced. In addition, GelMA gel was soft and extracellular matrix (ECM) alike, which was beneficial to decrease impairment to CTCs during the CTCs-barcode interaction as well as preserving their viability. Demonstrated by four CTCs types, Hela (epithelial tissue, folate receptor positive, FR+), A02 (bone marrow, FR+), Raji (lymphoid tissue, FR+), and A549 (epithelial tissue, folate receptor negative, FR-), FR+ CTCs could be captured efficiently with reliability and specificity. The captured cells could be controllably released with high viability just by quick trypsinization. The whole processes were simple and efficient. These features indicated that the FA-functionalized hybrid photonic barcodes were promising for full recovery of CTCs from cancer patients, which was important for diagnosis and treatment of cancer.

CAS / MDL: 59-30-3
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Materials Chemistry Frontiers · 2018 ·Vol. 2 ·期 8 ·1529-1538 · IF 0

Folate-conjugated and pH-triggered doxorubicin and paclitaxel co-delivery micellar system for targeted anticancer drug delivery

Lijing Niu,Feiyan Zhu,Bowen Li,Lingling Zhao,Hongze Liang,Yinghua Yan,Hui Tan

A folate-conjugated and pH-sensitive polymeric micellar system for the co-delivery of DOX and PTX was studied. A doxorubicin conjugated prodrug was synthesized via Schiff's base reaction. Subsequently, folate was grafted onto the prodrug and PTX was encapsulated. Sustained drug release of both DOX and PTX from the polymeric micelles was observed and the release rate could be accelerated by decreasing the media pH. A cellular uptake assay revealed that the polymeric micelles were internalized in the cytoplasm via endocytosis by SW1353 cells, and the cellular uptake was enhanced for the folate-conjugated micelles due to an active FR-mediated endocytosis pathway, showing stronger red fluorescence compared to that of non-folate micelles. The in vitro anticancer efficiency of the polymeric micellar system was evaluated using a cytotoxicity assay by incubating different drug formulations with the SW1353 cells. Both free drugs and micellar formulations displayed inhibition of cell growth at different levels, while the folate-conjugated dual-drug loaded polymeric micelles (Folate–Oxd–DOX/PTX) displayed a much lower IC50 value than other drug formulations, indicating a desirable in vitro anticancer efficiency due to the synergistic effect of co-delivery and active targeting. Thus, the polymeric micellar system is a promising platform for targeted cancer chemotherapy.

CAS / MDL: 59-30-3
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY · 2018 ·Vol. 18 ·期 6 ·4196-4203 · IF 1.354

High Quality Nitrogen and Silicon Co-Doped Carbon Dots (N/Si-CDs) for Fe3+ Sensing

Wu Jinzhu,Feng Yaxiu,Shao Yanbin,Sun Yanchun

Nitrogen and silicon co-doped carbon nanodots (N/Si-CDs) were synthesized by one-step hydrothermal carbonization of folic acid and 3-aminopropyl trimethoxy silane with the assistance of glycerol. The resultant N/Si-CDs present intense excitation-independent photoluminescence (PL) emission owing to their monodisperse sizes and specific surface states. In comparison to nitrogen single doped CDs (N-CDs), the co-doped N/Si-CDs possess better PL properties following different emission manner due to the synergistic effects of the nitrogen and silicon dopants. Besides, the functionalized surfaces of N/Si-CDs endow them with superior solubility and stability. The as-synthesized N/Si-CDs demonstrate selective and sensitive fluorescence response to Fe3+, which could be explained by the PL quenching effects of Fe3+ on N/Si-CDs. Based on this finding, the quantitative analysis of aqueous Fe3+ by N/Si-CDs was established, showing good linearity in a range of 10 nM~45 μM and good sensitivity with a detection limit of 3.8 nM, so did for the detection of Fe3+ in fetal bovine serum (FBS) spiked samples. Therefore, the N/Si-CDs as a novel fluorescence probe hold promising for monitoring environmental and clinical Fe3+.

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